Cardiovascular diseases are leading causes of morbidity and mortality in developed countries. Despite modern advances in science and medicine, our understanding of the factors that contribute to the development of vascular dysfunction is incomplete. Progress in treatment will depend on elucidating the complex interactions of hormones, growth factors, inflammatory agents, and oxidative stress on cell proliferation, migration, and death both in the vasculature and in circulation. Recent developments in proteomic techniques provide a promising approach for determining protein changes associated with complex diseases and permitting thorough evaluation of molecular changes associated with vascular dysfunction. Proteomic studies have revealed novel, dynamic, complex, and subtle changes of intracellular processes that are associated with the abnormal regulation of vascular function. This review provides an overview on the progress of applying proteomics to vascular diseases. We will describe the application of proteomics to clinically important vascular conditions and highlight the potential of using proteomics to advance our understanding on the mechanisms that underlie vascular diseases.